Liver transplantation in precirrhotic biliary tract disease: Portal hypertension is frequently associated with nodular regenerative hyperplasia and obliterative portal venopathy

Chronic biliary tract disease is the third most common indication for orthotopic liver transplantation (OLT) in the United States. Most patients undergoing OLT for chronic biliary tract disease have end-stage liver disease associated with cirrhosis, but a minority are transplanted in the precirrhotic stage for indications that can include poor quality of life (eg, intractable pruritis or fatigue), recurrent ascending cholangitis, or cholangiocarcinoma. A smaller subset of these patients suffer from severe noncirrhotic portal hypertension that can be associated with histologic features of nodular regenerative hyperplasia (NRH) and/or obliterative portal venopathy. We reviewed 306 liver explants performed for chronic biliary tract disease at 2 institutions during 1995 to 2003 to identify patients who were transplanted in the precirrhotic stage. The following clinical data were recorded: age, sex, type of biliary tract disease, radiology, clinical symptoms, signs of portal hypertension, pretransplant shunting procedures, time between diagnosis and OLT, and primary indication for OLT. Histopathologic data included: explant weight, gross appearance, fibrosis stage (1 to 4), cholangitis, bile duct dysplasia, malignancy, portal vein thrombi, presence of NRH, and presence of obliterative portal venopathy. Twenty-six of 306 (8.5%) patients underwent OLT in the precirrhotic stage (12 females: 14 males, mean age of 46 y, age range 12 to 68 y). At explant, fibrosis stage ranged from 1 to 2 (portal and periportal fibrosis) to 3 (multiple bridging fibrosis). Underlying biliary tract disease included primary sclerosing cholangitis (18 cases), primary biliary cirrhosis (5 cases), autoimmune cholangitis (2 cases), and secondary sclerosing cholangitis (1 case). Primary indications for OLT were recurrent cholangitis and/or decreased quality of life (11 cases), complications of portal hypertension (6 cases), portal hypertension plus cholangitis/decreased quality of life (5 cases), and malignancy (4 cases). Of the 11 patients with portal hypertension as a major indication for transplant, 2 had undergone transjugular intrahepatic portal-systemic shunting and 3 others had portal vein thrombi. Histopathologically, NRH was prominent in 8 of these 11 patients (73%) and obliterative portal venopathy in 6 (55%). NRH was also present in 4 of the 15 (27%) patients who were transplanted for other indications. These results indicate that precirrhotic portal hypertension is a predominant or major contributing factor to OLT in a significant minority (11 of 306, 3.3%) of patients with chronic biliary tract disease. The occurrence of NRH in some patients transplanted for other indications suggests it is a histologic pattern that can precede the development of clinically significant portal hypertension.     

肝结节性再生性增生18例诊治分析

目的 分析总结肝结节性再生性增生(nodular regenerative hyperplasia of the liver,NRH)的临床诊治经验,以提高临床医师对本病的认识.方法 回顾性分析我院近26年连续收治的18例:NRH的临床表现、影像学及实验室检查、诊治及预后资料.结果 本组18例NRH患者中有15例表现为门静脉高压,4例表现为肝脏单发、多发占位,8例合并自身免疫疾病,3例可疑合并血液系统疾病.本组患者中术前13例被诊断为肝硬化,2例诊断为肝癌或局灶性结节性增生(focal nodular hyperplasia FNH).所有18例患者均行肝楔形活检,并且3例行脾切除,4例行断流术/Phemister术,3例行肝占位/肝叶切除术,1例行部分小肠切除术,1例行脾动脉缩窄限流手术.术后门静脉高压症状明显缓解.随访多数患者症状稳定,说明肝脏占位的:NRH患者预后良好.结论 NRH可能与肝脏血供紊乱有关,临床最常表现为门静脉高压,并可伴发免疫、血液系统性疾病.临床表现为单发、或多发性肝脏占位,应注意与肝硬化、局灶性结节性增生、特发性门静脉高压等鉴别,诊断依靠肝楔形活检.手术对于治疗门静脉高压疗效确切.

Abstract：

Objective To summarize the clinical diagnosis and treatment of nodular regenerative hyperplasia of the liver. Methods Retrospective analysis was made on the clinical manifestations,imagings, laboratory tests, diagnosis, treatment and prognosis of 18 consecutive cases finally established as NRH during the past 26 years. Results 15 of the 18 cases showed portal hypertension, 4 cases showed mono or multiple occupations of the liver, 8 cases suffered from concurrent autoimmune diseases, 3 cases were suspected of blood diseases. Preoperatively, 13 cases were diagnosed as cirrhosis, 2 cases were diagnosed as liver cancer or focal nodular hyperplasia ( FNH). All cases were diagnosed by operative wedging biopsy. 3 cases received splenectomy, 4 cases received disconnection /Phemister surgery, 3 cases received liver occupation/liver lobe resection, 1 case received partial small bowel resection, and 1 case received spleen artery restrictive surgery. Postoperatively, symptoms of portal hypertension relieved obviously. Follow-up study showed most of the patients were stable and prognosis of the NRH was good.Conclusions NRH may relate to the disturbance of liver blood supply, and most common clinical manifestation is portal hypertension, and can combine with immune diseases, hematopathy also can present single or multiple liver occupations. Differential diagnoses include liver cirrhosis, FNH, idiopathic portal hypertension. Diagnosis of NRH relies on liver wedging biopsy. Surgery can relive concurrent portal hypertension.     

Significance of nodular regenerative hyperplasia occurring de novo following liver transplantation.

Nodular regenerative hyperplasia (NRH) of the liver usually occurs in patients with rheumatological and myelolymphoproliferative disorders; the occurrence post-liver transplantation (LT) has traditionally been ascribed to the use of azathioprine. We report the clinical, biochemical, and radiological features of 14 patients who developed NRH, unrelated to azathioprine in most cases, 3 months to 11 yr after orthotopic LT. A total of 10 patients developed NRH within 4 yr (early onset), and 4 other patients developed the condition beyond 4 yr of LT (late onset). A total of 7 symptomatic patients, all in the early group, had features of portal hypertension with vascular abnormalities on Doppler ultrasonography that were preceded by the diagnosis of NRH. All asymptomatic patients, including each of the 4 patients in the late group, had normal hepatic ultrasound (US) studies. Two symptomatic patients had normalization of histologic abnormalities after correction of vascular abnormalities. In conclusion, observation is appropriate for patients who develop NRH late following LT. Patients in whom NRH is detected on liver biopsy early after transplantation are likely to develop portal hypertension in the future. Intervention aimed at correcting the vascular abnormalities in these patients may result in clinical as well as hepatic histological improvement.     

Abnormal intrahepatic portal vasculature in native and allograft liver biopsies: a comparative analysis

Abnormal portal vessels in small portal tracts can be seen in association with various causes of portal hypertension, such as noncirrhotic portal hypertension (NCPH) and cirrhosis. Very little has been reported about the presence of abnormal portal vessels in livers with normal portal pressure. Little attention has also been given to the presence of abnormal vessels in liver allografts outside the setting of transplant vasculopathy/chronic rejection. This study reports on the portal vasculature abnormalities, many similar to those described in NCPH, encountered in routine native liver biopsies (n = 46) and allograft liver biopsies (n = 48). A classification scheme for the abnormal portal vasculature was adapted from the literature, and the portal vessels were divided into five groups (types 0-IV). Abnormal vessels were present in greater than 25% of the portal tracts in 88% of all the biopsies studied; there was no significant difference between the native and allograft biopsies. In the allograft biopsy group, there were correlations between vascular abnormalities and severity of a concurrent acute cellular rejection episode, the presence of prior rejection episodes, and length of time after transplant. Biopsies from patients with viral hepatitis C infection (HCV) showed more type IV lesions (absent or sclerosed portal vessels) with fragmentation when compared with biopsies obtained for other reasons. The number of portal tracts with abnormal portal veins and fragmented vessels correlated positively with increasing fibrosis. This is the first study to demonstrate the presence of abnormal portal vessels, some of the type seen in NCPH, in a significant number of both native and allograft liver biopsies in patients without evidence of portal hypertension. Abnormal portal vasculature tends to be associated with HCV and increased fibrosis, and, within the transplant group, with the severity of rejection, presence of prior rejection episodes, and increased time posttransplantation.     

Hepatopulmonary syndrome in children – is conventional liver transplantation always needed?

Willis AD, Miloh TA, Arnon R, Iyer KR, Suchy FJ, Kerkar N. Hepatopulmonary syndrome in children – is conventional liver transplantation always needed?
Clin Transplant 2011: 25: 849–855. © 2010 John Wiley & Sons A/S. Abstract: Background: Hepatopulmonary syndrome (HPS) is the association of liver disease, hypoxemia, and intrapulmonary vascular dilatations. There are little data on the management of HPS in children other than conventional orthotopic liver transplantation (OLT). Aims: To describe the patient characteristics, mode of diagnosis, treatment, and outcomes of children with HPS at our center. Methods: Retrospective review of patients diagnosed with HPS between 1997 and 2007 after IRB approval. Results: There were 10 patients, six females; median age at diagnosis of HPS was 12 yr. Six with cirrhosis underwent OLT and had subsequent resolution of HPS and are stable at last follow‐up. Of the remaining four, two had cirrhosis. HPS resolved without conventional OLT in the following four patients: hepatitis C after antiviral treatment, biliary atresia with portal hypertension after transjugular intrahepatic portosystemic shunting, Abernethy syndrome after auxiliary partial OLT, and in a child with splenic vein thrombosis after splenectomy. Conclusions: Our series shows resolution of HPS in all patients and 100% survival after conventional OLT. Four children had resolution of HPS after surgical or medical treatments other than conventional OLT. Careful review of clinical status and underlying pathophysiology and anatomy at diagnosis of HPS should inform treatment decisions.     

Influence of coexisting cirrhosis on outcomes after partial hepatic resection for hepatocellular carcinoma fulfilling the Milan criteria: an analysis of 293 patients

BACKGROUND: For patients with liver cirrhosis and hepatocellular carcinoma (HCC) satisfying the Milan criteria (single tumor < or =5 cm or 2 or 3 tumors < or =3 cm), orthotopic liver transplantation (OLT) is an effective treatment. Nevertheless, it remains controversial whether OLT is the best treatment strategy for patients with resectable HCC. METHODS: This study included 293 HCC patients (both with and without cirrhosis) oncologically satisfying the Milan criteria who underwent primary and curative liver resection between 1990 and 2003. RESULTS: There were 127 noncirrhotic, 129 Child-Pugh A cirrhotic, and 37 Child-Pugh B cirrhotic patients. Five-year survival rates in each population were 81%, 54%, and 28%, respectively. Coexisting cirrhosis, Child-Pugh classification, alpha-fetoprotein value, tumor burden, and vascular invasion by the tumor were identified as significant prognostic factors. Among these factors, coexisting cirrhosis was the most crucial variable by multivariate analysis. During the initial 3 postoperative years, yearly tumor recurrence rate was 22% in cirrhotic patients and 15% in noncirrhotic patients. In cirrhotic patients, the recurrence rate did not decrease even after three years of tumor-free survival post-resection, whereas in noncirrhotic patients the recurrence rate decreased to 9%. Cirrhosis was associated with a higher probability of recurrence exceeding the Milan criteria. CONCLUSIONS: Hepatic resection offers an acceptable survival result for HCC patients fulfilling the Milan criteria. Coexisting cirrhosis is associated with higher mortality and recurrence rate, possibly due to multicentric carcinogenesis which limits the efficacy of hepatic resection.     

Surgical complications accompanying liver transplantation in Estonia

The purpose of this study was to evaluate surgical complications accompanying the introduction of orthotopic liver transplantation (OLT) in Estonia. Between 1999 and 2009, we performed the first 12 liver transplantations. Eight patients were males and four were females of age range 12 to 67 years. Their diagnoses were cholestatic disease (n = 5); tumor (n = 3); hepatitis C virus cirrhosis (n = 2); Budd-Chiari syndrome (n = 1); and cystic fibrosis (n = 1). Technical complications occurred in 7/12 patients. The early vascular complications in two patients were a suprahepatic vena cava lesion occurring at liver extraction, which resulted in uncontrolled suprahepatic bleeding after liver perfusion; the recipient died during transplantation. The other case displayed a right intrahepatic portal venous thrombosis, which was treated successfully with thrombolysis and anticoagulant therapy. Early biliary complications of biliary leaks occurred in three patients: two had undergone duct-to-duct reconstructions, which were treated by endoscopic retrograde cholangiography that successfully managed the anastomotic and recipient cystic duct leaks with a papillotomy and stenting. In one patient with a duct-to-jejunum anastomosis, a bile leak stopped at 3 weeks but he needed surgical therapy 2 years later due to an anastomotic stricture. Severe decubitus occurred in the lumbosacral region of the subjects with operating times of 14 hours. They required necretectomy and plastic surgery. One of them with postoperative intra-abdominal hypertension also displayed wound eventration requiring reoperations. The rate of hepatic (5/12) and extrahepatic (3/12) surgical complications, as well as of 1-year survival (9/12), in our period of implementation of OLT were satisfactory to continue OLT development in Estonia.     

Orthotopic liver transplantation in case of TIPS stent dislocation

Transjugular intrahepatic portosystemic shunts (TIPS) are indicated in patients with liver cirrhosis and portal hypertension for treatment of variceal bleeding or refractory ascites. Additionally implantation of stents may lead to stent dislocation or thrombosis in up to 20 % of cases. Detailed information about stent dislocation and its impact on subsequent orthotopic liver transplantation (OLT) is rare regarding the literature. We report on a patient suffering from ethyltoxic liver cirrhosis in which OLT was technically complicated by a thrombosed TIPS stent, dislocated in the portal vein. This stent was implanted prior to OLT due to refractory ascites and partial portal vein thrombosis. We conclude that TIPS stent insertion, especially in liver transplant candidates, should only be performed by radiologists in centers with expertise and experience.     

Liver failure and need for liver transplantation in patients with advanced hepatoportal sclerosis

Hepatoportal sclerosis (HPS) is one of the causes of noncirrhotic portal hypertension. In general, hepatic synthetic function is preserved and treatment is aimed at relief of the portal hypertension. In this study, we present the clinical and pathologic features of HPS cases who underwent liver transplantation (LT). LT cases with confirmed gross and microscopic diagnosis of HPS are included. Weight of the explanted liver, presence of thrombi in the main blood vessels, and gross and microscopic characteristics were assessed. Clinical information was gathered from chart review. From 1995 to 2004, 8 LT patients were diagnosed with HPS. Cirrhosis resulting from alcohol (2), autoimmune hepatitis (2), and hepatitis B (1), or cryptogenic cirrhosis (3) was the presumed diagnoses pre-LT. Seven patients presented with bleeding varices and 5 had concomitant ascites. At the time of LT, mean values were: prothrombin time of 15.2 seconds, serum albumin 3.2 g/dL, serum bilirubin 3.5 mg/dL, alkaline phosphatase 140 IU/L, aspartate aminotransferase 39.4 IU/L, and alanine aminotransferase 34.7 IU/L. Explanted livers were shrunken, with weights ranging from 715 to 1199 g (mean 934). Nonocclusive portal vein thrombosis was present in 2 patients. On histologic examination, there was dense portal fibrosis, marked phlebosclerosis, and presence of variable degrees of megasinusoid formation. Four livers also had features of incomplete septal cirrhosis. None showed histologic features of the presumed underlying liver disease. In conclusion, HPS can cause hepatic synthetic dysfunction that may necessitate LT. Small liver volume, significant portal fibrosis, and phlebosclerosis may contribute to hepatic parenchymal loss and subsequent synthetic compromise.     

Liver transplantation for hepatopulmonary syndrome due to noncirrhotic portal hypertension

Background

Hepatopulmomary syndrome is defined by the triad of chronic liver disease, increased alveolar-arterial gradient, and evidence of intrapulmonary vasodilation. It is commonly seen in association with cirrhosis (90%). Four percent to 8% of the hepatopulmomary syndrome cases are reported in noncirrhotic portal hypertension. The management of patients with hepatopulmomary syndrome due to noncirrhotic portal hypertension is not well described.

Methods

We report a case of a 26-year-old woman who underwent liver transplantation for hepatopulmomary syndrome due to noncirrhotic portal hypertension. The patient presented with dyspnea and platypnea, requiring home oxygen therapy. She had orthodexia, severe hypoxemia, and positive bubble echocardiography consistent with hepatopulmomary syndrome. Her Model for End-stage Liver Disease score was 10. Liver biopsy revealed diffuse nodular regenerative hyperplasia.

Results

The patient underwent liver transplantation with Model for End-stage Liver Disease exception points. Her oxygen requirements gradually improved during the postoperative period. The patient's symptoms and hypoxemia resolved at 15-month follow-up posttransplantation.

Conclusion

We suggest hepatopulmonary syndrome in this setting is an indication for liver transplantation despite the absence of cirrhosis.     

Biliary-Venous Fistula Complicating Transjugular Intrahepatic Portosystemic Shunt Presenting With Recurrent Bacteremia, Jaundice, Anemia and Fever

A 50-year-old White man with noncirrhotic portal hypertension presented with bleeding from gastric varices. Bleeding was initially managed with band ligation and subsequent transjugular intrahepatic portosystemic shunt (TIPS). Over the next few months, the patient had recurrent episodes of anemia, jaundice, fever and polymicrobial bacteremia. Computed tomography (CT) of the abdomen and chest, upper and lower endoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and echocardiography failed to explain the bacteremia and anemia. Follow-up CT scan and Doppler sonography 9 months after placement showed TIPS was occluded. Repeat ERCP showed a bile leak with free run-off of contrast from the left hepatic duct into a vascular structure. The patient's status was upgraded for liver transplantation with Regional Review Board agreement and subsequently received a liver transplant. Gross examination of the native liver demonstrated a fistula between the left bile duct and the middle hepatic vein. Pathologic evaluation confirmed focal necrosis of the left hepatic duct communicating with an occluded TIPS and nodular regenerative hyperplasia consistent with noncirrhotic portal hypertension. Infection is rarely reported in a totally occluded TIPS. Biliary fistulas in patent TIPS have been treated by endoluminal stent graft and endoscopic sphincterotomy with biliary stent placement. Liver transplantation may be the preferred treatment if TIPS becomes infected following its complete occlusion.     

Results of resection and transplantation for hepatocellular carcinoma in cirrhosis and noncirrhosis

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Both liver resection (LR) and orthotopic liver transplantation (OLT) are surgical treatment options depending on the size of the tumor and the presence of cirrhosis. Liver cirrhosis is the main reason for the high early postoperative mortality after resection. Even in the Child A stage, extensive resections are not recommended. This study presented the results of surgical treatment (LR or OLT) for HCC in cirrhotic and noncirrhotic livers. We analyzed the data of 76 patients who underwent LR or OLT for HCC from January 2001 to December 2006. In noncirrhotic livers the following resections were performed: 30 right and extended right hemihepatectomies (54.5%); 11 left hemihepatectomies (20%); and 14 mono- or bisegmentectomies (25.5%). In cirrhotic livers the following procedures were performed: in Child A stage 1 right hemihepatectomy, 1 extended right hemihepatectomy, 1 extended left hemihepatectomy, and 4 mono- or bisegmentectomies; and in Child B stage, 3 mono- or bisegmentectomies. Among 11 patients who underwent transplantation, tumors in 2 patients exceeded the Milan criteria. Five patients in the LR group were treated with transarterial chemoembolization before transplantation. LR for HCC in cirrhosis should be performed with caution; there were no long-term survivors in our data. Our study confirmed that OLT shows good long-term survival in early HCC stages. However, this may also be true for stages above the Milan criteria. For HCC in noncirrhotic livers, LR remains the treatment of choice, justifying an extensive surgical approach. Such an approach achieved favorable long term survivals.     

肝硬化鼠肝移植后早期全身和内脏血流动力学的变化

目的 观察正常鼠肝移植及及肝硬化鼠肝移植术早期全身和内脏血流动力学的变化。方法 实验动物随机分为正常鼠（NL,10只）、肝硬化鼠（IHPH,10只）、正常鼠肝移植（NL－OLT,9只）、肝硬化鼠肝移植（IHPH－OLT,16只）组。分别采用放射性微球法行血流动力学研究。结果 NLOLT鼠绝大多数血流动力学参数与NL鼠比较差异无显著意义。IHPH及IHPH－OLT 3d,7d组心输量和内脏血流量和内脏血流量增加,平均动脉压、周围血管总阻力和内脏血管阻力降低。内脏血流动力学紊乱较全身明显。结论 肝硬化鼠肝移植后的血流动力学紊乱可能与移植前已存在的病理生理因素有关。     

Partial nodular transformation in a cirrhotic liver

We present a case of partial nodular transformation (PNT) of the liver in a 57-year-old man with a history of heavy drinking. On computed tomography, a low-density mass, measuring 3 cm in diameter, and associated with portal flow defect was visualized. Based on this finding and on the findings of other imaging studies, hepatic resection was performed because of suspected hepatocellular carcinoma. Pathology examination of the excised specimen showed small portal tracts in the lesion. The findings for the rest of the liver were suggestive of mild liver cirrhosis. While PNT is similar to nodular regenerative hyperplasia (NRH), in NRH there is diffuse nodular transformation of the whole liver, whereas in PNT only the area adjacent to the porta hepatis is affected. The portal flow defect in PNT may be the result of attenuation of the portal tracts in the lesion. This case is of interest because there was only one PNT lesion, rather than multiple lesions, and because it occurred in a cirrhotic liver, thus giving rise to the suspicion of hepatocellular carcinoma. PNT is a benign disorder, thus it is essential to establish a definitive diagnosis by imaging and ultrasound-guided histological biopsy to prevent unnecessary hepatic resection.     

Anaesthetic considerations in progressive familial intrahepatic cholestasis (Byler’s disease)

Progressive familial intrahepatic cholestasis (PFIC) or Byler’s disease is one of the most common forms of intrahepatic cholestasis of metabolic and genetic origin. Affected children progress to terminal cirrhosis before adulthood and at present the only curative treatment of PFIC is orthotopic liver transplantation (OLT). We present a retrospective review of 40 general anaesthetics administered in our hospital to 22 patients with PFIC undergoing various procedures. The clinical features of PFIC and the anaesthetic implications of chronic cholestasis in children (malnutrition, cirrhosis, portal hypertension, chronic hypoxaemia) are reviewed.     

Portal flow augmentation for liver cirrhosis

BACKGROUND: Portal hypertension due to chronic liver disease is a major cause of death worldwide. Orthotopic liver transplantation offers the best therapeutic option but is available to only a minority of patients. In the past few years mechanically pumping portal venous inflow has been reported to reduce portal hypertension and improve liver function. METHODS: A review of the published data on augmented portal perfusion for the treatment of portal hypertension in cirrhosis was carried out by searching Medline and other online databases. From each published study portal pressure and blood flow data before and after augmented portal perfusion were used to calculate the change in mean intrahepatic portal vascular resistance (IHPR). The standardized data were then combined to allow meta-analysis. RESULTS: Seven papers were identified on normal and cirrhotic animal and human livers with augmented flow (50% to fourfold over baseline) for 30-180 min. Meta-analysis revealed that the increased portal venous inflow was associated with a significant rise in portal venous pressure on the hepatic side (P < 0.001), a significant reduction on the mesenteric side (P < 0.001) and a significant reduction in IHPR (P = 0.013). Limited data were available to support improved liver function. CONCLUSION: Detailed in vivo cirrhotic liver studies on augmented portal flow in experimental models assessing haemodynamic and functional changes are required before clinical evaluation.     

Graft interposition splenocaval shunt for total or selective decompression of portal hypertension

A new operation for selective or total decompression of the portal venous system in cases of intrahepatic portal hypertension is described. It involves interposition of a large-caliber Dacron graft between the splenic vein and the inferior vena cava. The graft-interposition splenocaval shunt is performed readily and quickly, satisfying the variable hemodynamic needs of patients with portal hypertension. It can be either selective (S-SCS) or total (T-SCS) from the beginning, or a T-SCS may be converted subsequently to a S-SCS should surgically induced hepatic decompensation supervene. It is less demanding technically than distal splenorenal shunt (D-SRS). The S-SCS conserves portal venous perfusion of the liver, preserves hepatocellular function and architecture at the preoperative levels, avoids precipitation of postshunt portal-systemic encephalopathy, and decompresses gastric-esophageal varices with prevention of further variceal bleeding even better than D-SRS. One hundred percent graft patency has been obtained, and the surgical results have been superior to those following portacaval shunt in patients with large liver blood flow and relative benignity of the liver disease, be it cirrhosis or noncirrhotic portal fibrosis. In patients with advanced cirrhosis, variceal bleeding, and small liver blood flows, T-SCS would be indicated. Patients of this category obtained inferior surgical results and had operative deaths (16.7%) following S-SCS. The concept of the operation has merits and deserves further evaluation.     

Primary sclerosing cholangitis: role of extrahepatic biliary resection

BACKGROUND: Most centers advocate orthotopic liver transplantation (OLT) for patients with primary sclerosing cholangitis (PSC) and cirrhosis. Management of PSC patients without cirrhosis remains controversial. We examined the results of extrahepatic biliary resection (EHBR) for PSC. STUDY DESIGN: Between 1981 and 2006, 126 patients with PSC underwent EHBR (n = 77) or OLT (n = 49). Data on biliary drainage procedures, perioperative morbidity, and longterm survival were collected and analyzed. RESULTS: Of 77 patients undergoing EHBR, mean preoperative bilirubin level was 5.6 mg/dL. Nine (11.7%) patients had cirrhosis. Most patients had preoperative biliary drainage (ERCP, 61.0%; PTC, 67.5%). At operation, 73 (94.8%) patients underwent EHBR, including hepatic duct bifurcation. Most patients also had insertion of bilateral transhepatic silicone elastomer biliary stents; 4 (5.2%) underwent EHBR with stent insertion plus hepatectomy. For EHBR patients, perioperative complication rate was 38.7% and 30-day mortality was 3.9%. Bilirubin levels significantly decreased postoperatively (mean drop 3.8 mg/dL; p < 0.01). At 3 years, 57.1% of patients had no PSC-related readmissions, and 16.2% had more than 3. At a median followup of 10.5 years, 5- and 10-year survival was 76.4% and 52.7%, respectively. Cholangiocarcinoma did not develop in any patients, and only seven required OLT. Factors associated with worse survival included postoperative bilirubin >or= 2 mg/dL and history of cirrhosis (both p < 0.001). In patients undergoing EHBR, noncirrhotic patients had significantly better longterm outcomes versus cirrhotic patients (10-year survival, 60.2% versus 12.0%; p < 0.001). In contrast, 10-year survival of OLT patients with cirrhosis was 57.0%. CONCLUSIONS: Noncirrhotic patients with PSC can be successfully managed with EHBR. EHBR for noncirrhotic patients is associated with low perioperative morbidity, few readmissions, no new cholangiocarcinomas, and 10-year survival > 60%. OLT should be reserved for patients with PSC and associated hepatic cirrhosis.     

Kasai portoenterostomy--new insights from hepatic morphology

Background/Purpose

The aim of this paper was to investigate the mechanism of long-term biliary drainage after Kasai portoenterostomy by clinicopathologic study of hepatic morphology in explanted livers.

Methods

Explanted livers from 13 consecutive children undergoing transplantation for biliary atresia were examined in detail using a standardized protocol. Group 1 (n = 6) had no Kasai procedure before transplantation at a median age of 8 m. Group 2 (n = 4) were transplanted at a median age of 10 m after a failed Kasai portoenterostomy. Group 3 (n = 3) had a successful Kasai but required transplantation for complications of chronic liver disease at 12-14 years. Pathology findings were correlated with hepatic morphology determined by pretransplant magnetic resonance imaging.

Results

Large perihilar regenerative nodules (8-14 cm diameter) were observed in 2 patients after successful Kasai portoenterostomy, less well-defined perihilar nodules in group 2 patients, and no regenerative nodules in group 1. Microscopically, group 1 had diffuse biliary cirrhosis with evidence of progressive ductopenia during infancy. In group 2, perihilar regenerative nodules showed variable portal fibrosis but no cirrhosis and bile ducts were present with 68%-100% of hepatic arteries; in peripheral cirrhotic areas, bile ducts were absent in patients older than 9 m. The perihilar regenerative nodules in group 3 patients had a noncirrhotic architecture with preserved bile ducts, but the peripheral parenchyma was cirrhotic; one patient had diffuse macronodular cirrhosis. These morphologic findings correlated well with magnetic resonance images, highlighting the preservation of relatively normal perihilar liver architecture after successful Kasai portoenterostomy.

Conclusions

Unoperated biliary atresia is associated with progressive intrahepatic ductopenia leading to diffuse biliary cirrhosis. Kasai portoenterostomy can result in the growth of large perihilar regenerative nodules, probably as a consequence of surviving intrahepatic ducts in this region. In some patients, long-term success after Kasai portoenterostomy may depend on hyperplasia of the perihilar liver.     

Peginterferon and ribavirin in patients with HCV cirrhosis after liver transplantation

The objective of the study was to assess the efficacy of antiviral therapy in patients with hepatitis C virus (HCV) recurrence after liver transplantation (OLT). We included 30 patients of mean age 56 years, who experienced HCV recurrence after OLT. Mean time from OLT to the beginning of therapy was 57 months (median: 43 months). All of them were on monotherapy: tacrolimus (n = 21), cyclosporine (n = 6), and mycophenolate mofetil (n = 3). Fourteen had previously been diagnosed with allograft HCV cirrhosis. Patients were treated with peginterferon alpha 2b (1.5 mug/kg/weekly SC) and ribavirin (10.6 mg/kg/d) for 48 (genotypes 1, 4) or 24 weeks (genotypes 2, 3). After a mean follow-up of 20 months, two patients had died due to biliary sepsis (while on therapy) and acute myocardial infarction (7 months after the end of therapy). End of treatment virological response was achieved in 19 patients (63.3%) and sustained virological response (SUR) in 14 (46.7%). Comparing cirrhotic and noncirrhotic patients, SVR was achieved in seven patients in both groups (50% vs 43.8%; P = .732). Every patient had some adverse event; in 11 patients (36.7%) it was withdrawn (seven cirrhotic and four noncirrhotic; P < .05), and in 12 the starting dose was decreased (40%). There were neither rejection episodes nor cirrhotic complications during therapy, but infections were more common in cirrhotic patients (57% vs 25%; P < .05). In HCV cirrhotic transplanted patients the sustained virological response to combined antiviral therapy was similar to that in noncirrhotic patients, but severe adverse events including infections were much more common.